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411.
Mader M de Dios A Shih C Bonjouklian R Li T White W López de Uralde B Sánchez-Martinez C del Prado M Jaramillo C de Diego E Martín Cabrejas LM Dominguez C Montero C Shepherd T Dally R Toth JE Chatterjee A Pleite S Blanco-Urgoiti J Perez L Barberis M Lorite MJ Jambrina E Nevill CR Lee PA Schultz RC Wolos JA Li LC Campbell RM Anderson BD 《Bioorganic & medicinal chemistry letters》2008,18(1):179-183
Herein we report investigations into the p38alpha MAP kinase activity of trisubstituted imidazoles that led to the identification of compounds possessing highly potent in vivo activity. The SAR of a novel series of imidazopyridines is demonstrated as well, resulting in compounds possessing cellular potency and enhanced in vivo activity in the rat collagen-induced arthritis model of chronic inflammation. 相似文献
412.
Invasive pathogens threaten species recovery programs 总被引:1,自引:0,他引:1
413.
Roberto Valenzuela David Contreras Claudia Oviedo Juanita Freer Jaime Rodríguez 《International biodeterioration & biodegradation》2008,61(4):345-350
Metals can potentially play a role in the non-enzymatic processes involved in wood biodegradation. Dihydroxybenzenes reduce Cu(II)–Cu(I), which then react with H2O2 driving a Fenton reaction. In this work the degradation of veratryl alcohol (VA), the simplest non-phenolic lignin model compound, via a cuprous Fenton reaction mediated by 1,2-dihydroxybenzene (catechol, CAT) was studied. A factorial experimental design was performed to assess the impact of several experimental variables including, pH, and CAT, CuCl2 and H2O2 concentrations on VA degradation. Optimized conditions were determined using a response surface modeling methodology (RSM). The greatest amount of VA degradation occurred at a CAT:CuCl2:H2O2 ratio of 0.287:0.313:4.062, a pH of 3.6. A time-course measurement for VA degradation was performed under these experimental conditions and after an 8 h reaction period, 31% of the VA was degraded. Under the same experimental conditions, VA degradation by an iron CAT-driven Fenton reaction was more effective than the copper CAT-driven Fenton reaction. In a similar experiment, carboxymethyl cellulose (CMC) depolymerization was also determined. Only the iron CAT-driven Fenton reaction was found to depolymerize CMC. We suggest that the greater redox potential of the Fe(III)CAT complex compared to the Cu(II)CAT complex would dictate that under most environmental conditions, degradation of VA would occur by the iron complex only. This research has important implications for the mechanisms of brown rot fungal degradation in wood because it eliminates a pathway that had previously been proposed as a mechanism explaining free radical generation in the oxidative depolymerization of cellulose in the cell wall. 相似文献
414.
Vieira NC Espíndola LS Santana JM Veras ML Pessoa OD Pinheiro SM de Araújo RM Lima MA Silveira ER 《Bioorganic & medicinal chemistry》2008,16(4):1676-1682
Two hundred fifteen compounds isolated from plants of Northeastern Brazil flora have been assayed against epimastigote forms of Trypanosoma cruzi, using the tetrazolium salt MTT as an alternative method. Eight compounds belonging to four different species: Harpalyce brasiliana (Fabaceae), Acnistus arborescens and Physalis angulata (Solanaceae), and Cordia globosa (Boraginaceae) showed significant activity. Among them, a novel and a known pterocarpan, a chalcone, four withasteroids, and a meroterpene benzoquinone were the represented chemical classes. 相似文献
415.
Abnormal electrophysiological activation in schizophrenics during a personal traits attribution task
Changes in personal identity have been described as a major component in the expression of schizophrenia. Considering current evidence that relates the cortical structures of the medial line with the self, we hypothesize that there are differences in the frontomedial electrophysiological activation in schizophrenics when compared to normal subjects during tasks that require this function. In an experimental design, 9 schizophrenic and 7 normal subjects participated in a personal traits attribution task regarding the attribution of the self, another person and a simple reading. Electric brain activity was recorded with a dense array of 128 electrodes, with evoked brain potentials being obtained for the three conditions. Considering the evoked potential morphology, repeated measures ANO VA were performed on the adaptive mean for the 180-230 ms time window (P200) in the frontomedial electrodes, with a group effect being found (F=5.352; p=0.038). Comparisons of the groups show that the schizophrenics presented less voltage in the seZ/condition (t=2.386; p=0.033). Although the results are not consistent with the hypothesis, it can be suggested that the early modulation of word-related meaning formation in a self-referential context could be affected in schizophrenia. 相似文献
416.
417.
The genus Penicillium is one of the largest and widely distributed fungal genera described to date. As a result, its taxonomic classification and
species discrimination within this genus has become complicated. In this study, 52 isolates that belonged to the Penicillum genus and other related genera were characterized using two DNA-based methods: (i) analysis of the nucleotide sequences of
internal transcribed spacers in ribosomal DNA and (ii) analysis of DNA fingerprints that were generated by polymerase chain
reactions with specific primers for enterobacterial repetitive intergenic consensus (ERIC) and repetitive extragenic palindromic
(REP) sequences, and BOX elements. Using both methods, Penicillium species were discriminated from other fungal genera. Furthermore, Penicillium species that include strains which are used as biocontrol agents, such as P. glabrum, P. purpurogenum, and P. oxalicum, could be distinguished from other Penicillium species using these techniques. Based on our findings, we propose that a polyphasic approach that includes analysis of the
nucleotide sequences of ribosomal DNA and detecting the presence of highly conserved, repeated nucleotide sequences can be
used to determine the genetic relationships between different Penicillium species. Furthermore, we propose that our results can be used as a start point to develop a strategy to monitor the environmental
presence of particular strains of Penicillium species when they are used as biocontrol agents. 相似文献
418.
Dale O. Cowley Jaime A. Rivera-Pérez Mark Schliekelman Yizhou Joseph He Trudy G. Oliver Lucy Lu Ryan O'Quinn E. D. Salmon Terry Magnuson Terry Van Dyke 《Molecular and cellular biology》2009,29(4):1059-1071
Aurora-A is a conserved kinase implicated in mitotic regulation and carcinogenesis. Aurora-A was previously implicated in mitotic entry and spindle assembly, although contradictory results prevented a clear understanding of the roles of Aurora-A in mammals. We developed a conditional null mutation in the mouse Aurora-A gene to investigate Aurora-A functions in primary cells ex vivo and in vivo. We show here that conditional Aurora-A ablation in cultured embryonic fibroblasts causes impaired mitotic entry and mitotic arrest with a profound defect in bipolar spindle formation. Germ line Aurora-A deficiency causes embryonic death at the blastocyst stage with pronounced cell proliferation failure, mitotic arrest, and monopolar spindle formation. Aurora-A deletion in mid-gestation embryos causes an increase in mitotic and apoptotic cells. These results indicate that murine Aurora-A facilitates, but is not absolutely required for, mitotic entry in murine embryonic fibroblasts and is essential for centrosome separation and bipolar spindle formation in vitro and in vivo. Aurora-A deletion increases apoptosis, suggesting that molecular therapies targeting Aurora-A may be effective in inducing tumor cell apoptosis. Aurora-A conditional mutant mice provide a valuable system for further defining Aurora-A functions and for predicting effects of Aurora-A therapeutic intervention.The equal partitioning of chromosomes at mitosis is critical for avoiding aneuploidy, a condition associated with spontaneous miscarriage, developmental disorders, and cancer (50). Mitosis requires coordinated completion of multiple events including nuclear envelope breakdown, chromosome condensation and congression to the metaphase plate, centrosome separation, spindle formation, chromosome-spindle attachment and error correction, sister chromatid separation, and cytokinesis. Multiple regulators, many of which are kinases, are required to ensure that each event is completed in a timely fashion and in the proper order (reviewed in reference 46). Although a number of mitotic kinases have been identified, their targets and the intricacies of mitotic signal transduction pathways are just beginning to be understood.The Aurora kinases are key mitotic regulators in eukaryotes (reviewed in reference 45). The Aurora family includes a single member in yeasts (Saccharomyces cerevisiae Ipl1p, Schizosaccharomyces pombe Ark1), two members each in Caenorhabditis elegans and Drosophila, and two or three members in vertebrates. Although originally given a variety of names, Aurora kinases in multicellular eukaryotes have subsequently been classified into A, B, and C groups based on patterns of mitotic subcellular localization and homology, which also appear to reflect functional distinctions (8, 46). Aurora-A kinases are observed at centrosomes and adjacent spindle fibers, and current evidence supports key roles in regulating protein localization and function at centrosomes, as well as regulation of the assembly, stability, and function of the mitotic spindle (reviewed in reference 43). Aurora-B kinases display “chromosomal passenger” localization, residing on mitotic chromosomes and subsequently moving to the spindle midzone after separation of sister chromatids. Aurora-B family members have been implicated in the regulation of kinetochore-spindle attachment, the spindle checkpoint, and cytokinesis (reviewed in references 1 and 8). Aurora-C kinases, which have only been identified in mammals, have a limited expression pattern and appear to have functions that overlap those of Aurora-B (7, 53).The human Aurora-A kinase (hAurA) was first identified because of its overexpression in cancer cell lines (5, 58). The hAurA gene (stk15) resides on chromosome 20q13, a region frequently amplified in human cancers (5, 58). hAurA has been dubbed an oncogene because of the fact that its overexpression transforms immortalized rodent fibroblasts (5, 70). Polymorphisms in hAurA are associated with an increased risk of colon cancer, while murine AurA (mAurA) polymorphisms confer increased susceptibility to experimentally induced skin tumors (14). The mAurA gene is frequently amplified in radiation-induced lymphomas from p53 heterozygous mice, while loss of one mAurA allele has been observed in lymphomas from p53-null mice (41). Thus, aberrant AurA expression is associated with tumorigenesis, suggesting that insight into AurA functions will lead to a better understanding of tumorigenesis mechanisms.A number of experimental observations suggest that AurA kinases are required for normal centrosome maturation and bipolar spindle assembly. The AurA ortholog in Drosophila melanogaster (Aurora) was identified in a screen for mutations that impact the centrosome cycle (21). Syncytial embryos from hypomorphic Aurora mutant females display a variety of mitotic abnormalities resulting from a failure to separate centrosomes. Aurora-null flies die at the larval stage with characteristic monopolar spindles and circular chromosome arrays in larval neuroblasts. Such monopolar spindles arise from failed centrosome separation (21). Subsequent studies of Drosophila Aurora mutant alleles revealed additional defects in centrosome maturation (including a failure to localize transforming acidic coiled-coil protein, centrosomin, and γ-tubulin at centrosomes) and in asymmetric localization of Numb protein in sensory organ precursor cells (3, 17). Similar to the case in Drosophila, disruption of the C. elegans AurA ortholog AIR-1 by RNA interference (RNAi) or mutation causes defects in centrosome maturation and monopolar spindle formation. Centrosomes undergo normal separation but collapse, leading to monopolar spindle formation (16, 24, 56). Studies of the Xenopus AurA homolog pEg2 revealed similar phenotypes after overexpression of kinase-dead mutants, antibody-mediated inhibition, or immunodepletion (18, 19, 38, 52). Furthermore, Xenopus AurA has been shown to interact with and phosphorylate Eg5, a mitotic kinesin required for bipolar spindle formation, suggesting a possible mechanism by which AurA could influence bipolar spindle formation and/or stabilization (19). Thus, existing reports from these systems are quite consistent in implicating AurA in centrosome separation and function.In contrast to the systems described above, published reports of RNAi-mediated reduction of AurA expression in mammalian cell lines have contained conflicting results about the role of AurA in mitotic entry, bipolar spindle formation, and mitotic progression. AurA RNAi in HeLa cells was reported to block or delay mitotic entry, prompting the conclusion that AurA is essential for mitotic commitment in mammalian cells (27, 36). In contrast, other AurA RNAi studies showed accumulation of mitotic cells with monopolar spindles (12, 20, 67). These discrepancies call into question the functional conservation of AurA in mammals and highlight a need for additional studies to definitively address the roles of AurA. This is particularly critical for understanding the roles of AurA in cancer and for projecting possible effects of AurA inhibitors currently in development as anticancer agents. We used gene targeting in mouse embryonic stem (ES) cells to produce a conditional null allele at the AurA locus. Here we describe cellular phenotypes of AurA deletion in primary cells in vitro and developmental phenotypes of AurA mutant mice. We show that AurA deletion in primary embryonic fibroblasts causes delayed mitotic entry with accumulation of cells in early prophase, consistent with a role for AurA in mitotic entry. Nevertheless, AurA-deficient cells that enter prometaphase arrest with monopolar spindles and eventually exit mitosis without segregating their chromosomes. Prolonged culture of AurA-deficient cells leads to polyploidy with abnormal nuclear structure. Germ line AurA deficiency causes embryonic death at the blastocyst stage with mitotic arrest and monopolar spindle formation, while AurA deletion in mid-gestation embryos causes an increased mitotic index and increased apoptosis. Together, our findings indicate that AurA is required for timely mitotic entry and bipolar spindle formation in vitro and in vivo. 相似文献
419.
Ana Whyte Luis V. Monteagudo Angel Díaz-Otero M. Eugenia Lebrero M. Teresa Tejedor M. Victoria Falceto Jaime Whyte Margarita Gallego 《Animal reproduction science》2009,115(1-4):328-333
Persistence of the Müllerian duct syndrome (PMDS) is a rare form of pseudohermaphroditism characterized by the presence of uterus and oviducts in otherwise normally differentiated SRY-positive 78 XY canine males. Undescended testicles are also common. We report a case of a male PMDS dog with a uterus and bilateral cryptorchidism. The dog had an incomplete regression of the mesonephric tubules. As a consequence of this an abnormally enlarged head of the epididymis was observed. In addition, an extreme reduction in size of both the body and the tail was found. Microscopic examination of both testicles revealed bilateral hyperplasia of Leydig cells. The progesterone blood level was measured by ELISA and was found to be abnormally high (3.18 ng/ml) compared to that of normal male dogs (lower than 1 ng/ml). Three months after surgical removal of the internal genitalia, the serum progesterone, testosterone and oestradiol levels were normal for a castrated male dog. 相似文献
420.
De los Reyes M Palomino J de Lange J Anguita C Barros C 《Animal reproduction science》2009,110(1-2):37-45
The aim of this study was to evaluate the effect of sperm cryopreservation and the maturation state of the oocyte on the time course of canine gamete interaction during co-culture for periods of 1-10 h. Semen samples were obtained by digital stimulation and ejaculates processed as fresh, chilled and frozen samples. Sperm were co-cultured with immature or in vitro mature bitch oocytes for up to 10 h. At hourly intervals, oocytes were evaluated for sperm penetration with epifluorescence microscopy. The results were analyzed statistically using generalized linear models. Spermatozoa treatments had a significant effect on the total percentage of oocyte penetration for both types of oocytes; fresh spermatozoa showed the highest average penetration rate, while frozen sperm showed the lowest value (p<0.05). At the 1st hour of co-culture, chilled and frozen dog sperm had a higher penetration percentage (p<0.05) of in vitro matured canine oocytes (43.6% and 45.7%, respectively) than the fresh sperm had (33.8%). Sperm penetration was directly proportional to the time of incubation, when fresh or chilled sperm were used (P<0.05); in contrast, frozen dog sperm did not change penetration rates with either immature or in vitro matured oocytes over time. There was a significant difference in the average of penetration rate between immature (47.3%) and in vitro matured oocytes (56.6%) throughout the 10h of culturing; irrespective of sperm treatment. The optimal incubation time in terms of maximizing penetration rates probably are dependent on how spermatozoa were processed prior to fertilization. 相似文献